Drug delivering methods based on nanometer technologies in recent years have gained great attentions of researchers. Wherein, a nanometer micelle carrier system formed by self-assembly of amphiphilic block copolymer in an aqueous solution has become a new-type drug carrier having great application prospect. A methoxypolyethylene glycol-polylactic acid block copolymer is a biodegradable material, which can be widely applied to various dosage forms, and is finally degraded into carbon dioxide and water in a human body, and a methoxypolyethylene glycol-dl-polylactic acid block copolymer with a certain molecular weight can form a micelle. These micelles after being prepared into dosage forms with bulk drugs have the advantages of slow release, target, safety, easy absorption and small side effects.
A nano-polymer micelle is a drug carrier system developed in recent years directing to indissolvable drugs, which has a core-shell structure, wherein the core is a hydrophobic part, and the shell is a hydrophilic part. The polymer micelle may encapsulate the indissolvable drugs into the core part to solubilize the indissolvable drugs. Compared with a normal solubilizer and latent solvent, the polymer micelle drug carrier system has higher security since it selects biodegradable material as raw materials. Therefore, it has a better application prospect while being served as an encapsulating-carrying accessory for the indissolvable drugs.
There are two synthesis methods at present for preparing polyether and polyester block copolymers: one method is to add polyether into a pre-dried polymerization bottle and residual moisture in the polyether is removed by means of heating and evacuation, then lactone is added, and catalyst is added when the polyether and lactone are in a molten state, and the polymerization bottle is sealed for reaction. The method has the defects that a reaction system is unavoidably contacted with the outside during the process of adding the lactone and catalyst, which is extremely easy to bring the moisture in the air into the reaction system, while the lactone is easily hydrolyzed in the molten state. Another method is to use polyether to be directly polycondensed with lactic acid under high temperature to obtain a block copolymer, but it has defects that the polymerization activity of the lactic acid is lower, and a large number of lactic acid is remained in the final product, wherein the residual lactic acid monomer needs to be removed through multiple and repeated dissolution-precipitation; therefore, not only the final copolymer yield is lower, but also the stability between each batch of products is poorer, and harmful heavy metal catalyst cannot be effectively removed during the repeated precipitation process. Moreover, the product is easily oxidized and turns yellow because the polycondensation temperature is higher and the reaction time is longer. Patent 2011100637853 discloses a method for preparing medical polyether polyester block copolymer, which includes using sufficiently dried polyether to initiate ring opening polymerization of lactone under a vacuum condition to prepare a block copolymer, wherein a degree of vacuum is required to be less than 1 mm Hg, a polymerization process is controlled to be performed at a temperature more than 130° C., and a polymerization time is 1-12 hours (h); after the reaction is finished, un-reacted monomer remained in the product is removed through hydration, and the heavy metal catalyst is removed through a method of high speed centrifugation, so that a copolymer material with good molecular weight homogeneity is prepared. This copolymer while being used for carrying drugs effectively improves the solubility of indissolvable drugs, and improves the safety and efficacy of the drugs. However, it has defects that the stability after being dispersed by water is poorer, and drugs are leaked in a very short time, so that it cannot be further popularized and truly applied during clinic application since its physical stability is not high. In order to solve the problem, CN201010114289 discloses a technology which improves the stability of a micelle after re-dissolving through a method of adding amino acid in a polymer micelle, but the added substances have higher requirements on industrialized production, and a stabilizer added increases the technical complexity of the preparation, and meanwhile, the added amino acid plays a role of degrading the main drugs, which is not suitable for large-scale production.